Recent data suggest that the prevalence of physician-diagnosed systemic lupus erythematosus (SLE) is 6-10 fold greater than previous reports. SLE, which affects primarily young women in the prime of life, leads to increased mortality, chronic organ system damage, and a poor health status equivalent to that in HIV infection. The Baltimore Lupus Cohort is an ongoing, prospective study in which SLE patients are followed, by protocol, quarterly. It is racially balanced and reflects a wide socioeconomic range. Building on this 8 year database of demographic, social, clinical and laboratory measures, the current proposal will address three new areas. First, we will determine the predictive value for lupus activity/flare (using valid and reliable disease activity indices) of currently available serologic tests (C3, C4 anti-dsDNA by two assays) and investigational assays (complement split products) in longitudinal regression models that adjust for demographic, clinical, and treatment variables. Second, we will accrue sufficient outcomes to identify prospective risk factors for permanent organ damage, which often does not appear (as in the case of renal damage) for 10 years after diagnosis. This will include an assessment of markers of on-going coagulation to determine if these are predictors of those SLE patients with antiphospholipid antibodies at risk for thrombosis. To increase the power in analyses of risk factors for atherosclerosis, a surrogate outcome variable, carotid duplex, will be added. Finally, we will prospectively determine the predictors of health status and change in health status (emphasizing disease activity, organ damage, treatment variables, psychological constructs such as coping skills, and serial assessment of fibromyalgia). Understanding the basis of change in health status measures is necessary to justify the future use of these measures as efficacy outcomes in clinical trials.